Cannabis Use and the HIV Continuum of Care: Implications and Considerations

1. Does cannabis use complicate the HIV continuum of care? David J. Grelotti, MD Director of Mental Health Services, Owen Clinic Medical Director, University of California Center for Medicinal Cannabis Research Associate Professor of Psychiatry, UC San Diego School of Medicine January 24, 2019 Physicians: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint providership of the University of Nevada School of Medicine and the Pacific AIDS Education and Training Center. The University of Nevada, Reno School of Medicine is accredited by the ACCME to provide continuing medical education to physicians. The University of Nevada, Reno School of Medicine designates this live activity for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurses: Nurses may receive continuing education credit for this educational activity as the ANCC accepts AMA PRA Category 1 Credits™ through its reciprocity agreement.

2. Disclosures All presenters of this continuing medical education activity have indicated that neither they nor their spouse/legally recognized domestic partner has any financial relationships with commercial interests related to the content of this activity.

3. Learning Objectives • To review the epidemiology of cannabis use • To evaluate current science on the relevance of cannabis to the HIV epidemic

4. Cannabis • 340 varieties of Cannabis plants • Millennia of use and cultivation • Inhaled or ingested for its psychoactive and therapeutic effects Lynch et al. 2015

5. Legalization of cannabis

6. Increasing prevalence of use • 2.7-4.9% 12-month adult prevalence globally • Possible relationship with liberalization of cannabis use laws UNODC, 2015; EMCDDA 2017; Garin et al. 2015

7. Question 1 The 12-month prevalence of cannabis use among PLWH is estimated to be: • Less than 10% • 30-40% • Greater than 60%

8. Prevalence of use in HIV (USA) • 15% 1-month prevalence • Veterans; 2002-2010 • 24.3% 3-month prevalence • HIV primary care clinics (CNICS); 2005-2008 • 38.1% 12-month prevalence • HIV primary care clinics; 2003-2005 • 34.9% 12-month prevalence • National survey; 2005-2015 • 62% lifetime prevalence • HIV primary care clinics (CNICS); 2007-2014 Hartzler et al. 2017; Mimiaga et al. 2013; Adams et al. 2018; Pacek et al. 2018

9. Cannabis use disorder • 9 – 10% of regular cannabis users • Growing proportion of first time entrants into treatment • Evidence-based treatment • Cognitive Behavioral Therapy • Motivational Enhancement Therapy • No significant impact of Screening, Brief Intervention, and Referral to Treatment (SBIRT) on cannabis “involvement scores” for PLWH EMCDDA 2017; Dawson-Rose et al. 2017

10. Cannabis use disorder in HIV • 31% estimated prevalence of a cannabis use disorder • HIV primary care clinics (CNICS); 2007 and 2014 • Wide variation in prevalence depending on (4%-52%) Hartzler et al. 2016

11. Cannabis use disorder Multiple comorbidities • Other substance use disorders (including tobacco use disorders) • Other mental health disorders • Mood disorders • Anxiety disorders • Psychotic disorders • Individual and community factors Pacek et al. 2018; Bruce et al. 2015

12. Cannabis-associated harms NAS 2017

13. Favorable clinical trials of cannabis NAS 2017

14. Question 2 True or False: People with HIV are more likely to use cannabis for its perceived health effects than to get “high.” • True • False

15. Medicinal cannabis use in PLWH Percent (%) Woodridge et al. 2005

16. What is the impact on the HIV continuum of care?

17. HIV transmission Factors reducing risk Factors increasing risk Youth, PLWH, heterosexual adults demonstrate more sexual risk behaviors (condomless sex, greater number of lifetime sexual partners) potentially mediated by: Decreased intentions to use HIV protection Lower self-efficacy Higher risk preference/hedonism Cardoso & Malbergier 2015; Brodbeck et al. 2006 Homeless youth and MSM who use cannabis have less injection drug use or longer times to initiation of injection drug use Reddon et al. 2018; Heinsbrook et al. in press

18. HIV transmission risk • Risky sex after controlled administration of 2.8% THC was considered less likely Metrik et al. 2012

19. HIV transmission Factors reducing risk Factors increasing risk Greater probability of viral shedding in semen of virally suppressed MSM who use cannabis during sex Ghosn et al. 2014 Lower HIV viral load among daily cannabis users newly diagnosed with HIV Milloy et al. 2015

20. Linkage and retention • No association with linkage to care (Lake et al. 2017) • Associated with missed clinic visits but not retention (Kipp et al. 2017; Tarantino et al. 2018)

21. ART adherence • No association with adherence in a majority of other studies (Rosen et al. 2013; De Jong et al. 2005; Soto Blanco et al. 2005; Vidot et al. 2017; Slawson et al. 2014) but not African American youth in the US. (Gross et al. 2016) • Cannabis dependence, but not cannabis use was associated with poorer adherence (Bonn-Miller et al. 2014) Rosen et al. 2013

22. Question 3 True or False: Plasma antiretroviral concentrations are unchanged in the setting of cannabis exposure. • True • False

23. Cannabis and ART • In vitro evidence of inhibition of CYP3A and SYP2C • Statistically significant reductions in indinavir (but not nelfinavir) concentrations in vivo suggests induction of P-450 enzymes Kosel et al. 2002

24. Viral suppression Results are mixed • Cannabis dependence, but not cannabis use was associated with higher viral load (Bonn-Miller et al. 2014) • Cannabis use was associated with lower rates of viral suppression (Kipp et al. 2017) • Cannabis use was associated with lower viral loads (Thames et al. 2015)

25. Cannabis and T-cells No impact on CD4 or CD8 count No impact on viral load Source: Abrams, et al. 2002 & 2003

26. Morbidity: Inflammation • Lower frequencies of activated (HLA-DR+CD38+) CD4+ and CD8+ T cells • Lower frequencies of TNF-α+ B cells • No differences in the frequency of IL-6+ B cells • Lower frequencies of IL-23+ and TNF-α+ antigen presenting cells Manuzak et al. 2018

27. Morbidity: Inflammation • Lower circulating CD16 monocytes and plasma IP-10 (implicated in neuroinflammation) among HIV+ cannabis users • In-vitro THC treatment impaired CD16 monocyte transition to CD16 and IP-10. Rizzo et al. 2018; Manuzak et al. 2018

28. Mortality • Cannabis use [b =-0.97 (95% CI -1.93, 0.00), p = 0.048] was not associated with 5-year mortality risk among 3099 veterans followed from 2002-2010 Adams et al. 2017

29. Summary • Associated with HIV transmission risk, but likely mediated by other factors • Possible association with poorer adherence or viral suppression in the setting of heavy use or dependence • Unlike other drugs, no association with mortality • Limitations of these studies include their observational nature, limited information on cannabinoid concentrations, dosages, routes of administration and possible contaminants

30. References • The Health Effects of Cannabis and Cannabinoids. National Academies of Sciences, Engineering, and Medicine (Free): • https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the-current-state • Monitoring Health Concerns Related to Marijuana in Colorado: 2016. State of Colorado (Free): • https://www.colorado.gov/pacific/cdphe/marijuana-health-report • Wilsey, et al. (2015) The Medicinal Cannabis Treatment Agreement: Providing Information to Chronic Pain Patients Through a Written Document. Clin J Pain. • The University of California Center for Medicinal Cannabis Research (Free / Link to Research): • http://cmcr.ucsd.edu • cmcr@ucsd.edu